The objective of this program is to gain further insight into changes in selected biochemical regulatory mechanisms during aging. One project addresses the regulation of insulin secretion and the action in Sprague-Dawley rats. A second project addresses the relationship between susceptibility of cultured skin fibroblasts to chemically induced mutagenesis and the lifespan of mammalian species from which the cells are derived. A third project concerns the integrity of the hepatic glucocorticoid receptor system throughout the lifespan of Sprague-Dawley rats.